PUBLICATION

Foxc1 establishes enhancer accessibility for craniofacial cartilage differentiation

Authors
Xu, P., Yu, H.V., Tseng, K.C., Flath, M., Fabian, P., Segil, N., Crump, J.G.
ID
ZDB-PUB-210128-24
Date
2021
Source
eLIFE   10: (Journal)
Registered Authors
Keywords
chromosomes, developmental biology, gene expression, zebrafish
Datasets
GEO:GSE157575
MeSH Terms
  • Animals
  • Cartilage/embryology
  • Cell Differentiation
  • Chondrocytes/metabolism
  • Chondrogenesis*
  • Embryo, Nonmammalian/embryology
  • Forkhead Transcription Factors/genetics*
  • Forkhead Transcription Factors/metabolism
  • Neural Crest/embryology
  • Skull/embryology*
  • Zebrafish/embryology*
  • Zebrafish Proteins/genetics*
  • Zebrafish Proteins/metabolism
PubMed
33501917 Full text @ Elife
Abstract
The specification of cartilage requires Sox9, a transcription factor with broad roles for organogenesis outside the skeletal system. How Sox9 and other factors gain access to cartilage-specific cis-regulatory regions during skeletal development was unknown. By analyzing chromatin accessibility during the differentiation of neural crest cells into chondrocytes of the zebrafish head, we find that cartilage-associated chromatin accessibility is dynamically established. Cartilage-associated regions that become accessible after neural crest migration are co-enriched for Sox9 and Fox transcription factor binding motifs. In zebrafish lacking Foxc1 paralogs, we find a global decrease in chromatin accessibility in chondrocytes, consistent with a later loss of dorsal facial cartilages. Zebrafish transgenesis assays confirm that many of these Foxc1-dependent elements function as enhancers with region- and stage-specific activity in facial cartilages. These results show that Foxc1 promotes chondrogenesis in the face by establishing chromatin accessibility at a number of cartilage-associated gene enhancers.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping